Current treatments for severe post-stroke arm impairment, a major contributor to stroke-related disability, are of limited efficacy and patients are often permanently disabled. While mechanisms of arm and hand recovery have been extensively studied, patients with impaired reaching movements and no hand function are often ex- cluded from these studies due to the severity of their impairment. Thus there is little known about mechanisms of arm recovery in the large proportion of the stroke population that has sustained more severe damage to the corticomotor system and lacks hand function. The long-term goal is to gain the mechanistic information needed to develop interventions to improve reaching ability in patients with severe corticomotor system damage. The objective in this proposal is to identify the role of the unaffected hemisphere (UH) in affected arm movements in this population. While UH activation is often considered deleterious to recovery, new models suggest that in those with less structural reserve, UH motor areas could contribute to motor recovery. Here, the central aim is to determine the extent to which UH motor areas can contribute to affected arm reaching movements in patients with severe corticomotor damage . The central aim will be achieved via 2 specific aims: 1) Compare the role of the unaffected vs. affected hemi- sphere in reaching movements of stroke patients with severe impairment, 2) Determine the effect of excitatory non-invasive brain stimulation to UH motor areas on practice-induced reaching improvements in patients with severe impairment. Under Aim 1, non-invasive brain stimulation will be used to momentarily interfere with pro- cessing in unaffected and affected hemisphere areas to see if it has any effect on movement of the affected arm. Under Aim 2, non-invasive brain stimulation will be used to induce a longer-lasting increase in excitability of the unaffected or affected hemisphere prior to a bout of reaching practice. We will compare the amount of improvement in reaching ability after stimulation of each targeted brain area. We will also test for any change in the role of the targeted brain areas in the movement. The approach is innovative because it addresses a little-studied topic (recovery mechanisms in severely im- paired patients) and targets brain areas that have been thought to be deleterious to recovery (UH). The pro- posed research is significant because, to develop interventions to improve post-stroke arm recovery, the mechanisms of impairment and recovery must be understood. Since a large portion of stroke-related disability is due to arm impairment, improvements in arm function could result in enormous benefits (and cost savings) when multiplied across this large and steeply growing population.